Patent EA-003771-B1 (EA)
Title: Propofol composition comprising pentetate
Inventor: GEORGE MARY MATHEW
IPC: A61K47/24
Filed: 1999-10-21
Abstract: 1. A sterile pharmaceutical composition for parenteral administration which comprises an oil-in-water emulsion of a lipophilic pharmaceutical agent and an amount of pentetate sufficient to prevent a no more than 10-fold increase in growth of each of Pseudoinonas aeruginosa, Escherichia coli, Staphylococcus aureus and Candida albicans for at least 24 hours after adventitious extrinsic contamination. 2. A sterile pharmaceutical composition for parenteral administration which comprises an oil-in-water emulsion of propofol and an amount of pentetate sufficient to prevent a no more than 10-fold increase in growth of each of Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus and Candida albicans for at least 24 hours after adventitious extrinsic contamination. 3. A sterile pharmaceutical composition for parenteral administration, which comprises an oil-in-water emulsion of propofol and not more than 0.1% by weight of pentetate. 4. A sterile pharmaceutical composition of claim 1 comprising from about 0.0005% to about 0.1% by weight of pentetate. 5. The sterile pharmaceutical composition of claim 1 comprising not more than 30% by weight of a water immiscible solvent. 6. The sterile pharmaceutical composition of claim 1 comprising from 10% to 20% by weight of a water immiscible solvent. 7. The sterile pharmaceutical composition of claim 6 where the water immiscible solvent is a vegetable oil or an ester of a fatty acid. 8. The sterile pharmaceutical composition of claim 7 where the water immiscible solvent is soybean oil. 9. The sterile pharmaceutical composition of claim 1 wherein the pH is about 6.5 to 9.5. 10. The sterile pharmaceutical composition of claim 14 comprising 1% to about 2% propofol. 11. The sterile pharmaceutical composition of claim 1 comprising about 1% propofol. 12. The sterile pharmaceutical composition of claim 1 comprising about 2% propofol. 13. The sterile pharmaceutical composition of claim 1 further comprising a surfactant. 14. The sterile pharmaceutical composition of claim 13 wherein the surfactant is a naturally occurring phosphatide. 15. The sterile pharmaceutical composition of claim 14 wherein the naturally occurring phosphatide is egg lecithin. 16. The sterile pharmaceutical composition of claim 13 wherein the surfactant is a non-naturally occurring phosphatide. 17. The sterile pharmaceutical composition of claim 1, which is isotonic with blood. 18. The sterile pharmaceutical composition of claim 17, which is isotonic with blood by incorporation of glycerin. 19. A sterile pharmaceutical composition in the form of an oil-in-water emulsion comprising: a) about 2% by weight of propofol; b) about 10% by weight of soybean oil; c) about 1.2% by weight of egg lecithin; d about 2.25% by weight of glycerin; e) about 0.0005% by weight pentetate; f) water to 100%. 20. A sterile pharmaceutical composition in the form of an oil-in-water emulsion comprising: a) about 1% by weight of propofol; b) about 10% by weight of soybean oil; c) about 1.2% by weight of egg lecithin; d) about 2.25% by weight of glycerin; e) about 0.0005% by weight pentetate; f) water to 100%. 21. A sterile intravenous fat emulsion comprising an amount of pentetate sufficient to prevent a no more than 10-fold increase in growth of each of Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus and Candida albicans for at least 24 hours after adventitious extrinsic contamination. 22. A sterile pharmaceutical composition for parenteral administration, which comprises the following steps: a) obtaining of oil phase, comprising a pharmaceutical agent and water-immiscible solvent; b) obtaining of aqueous phase, comprising a surfactant; c) homogenizing of oil phase and aqueous phase with obtaining concentrated emulsion; d) obtaining of aqueous composition of pentetate; e) adding of aqueous composition of pentetate to concentrated emulsion; f ) sterilization of emulsion. 23. A method of limiting microbial growth in a sterile oil-in-water emulsion pharmaceutical composition following extrinsic contamination of said sterile composition comprising incorporating into said oil-in-water emulsion an amount of pentetate sufficient to prevent an at least ten fold increase in the growth of microorganisms for at least twenty-four hours after extrinsic contamination.